TY - JOUR
T1 - 2-Arylidene Hydrazinecarbodithioates as Potent, Selective Inhibitors of Cystathionine γ-Lyase (CSE)
AU - Bhattacharjee, Abir
AU - Sinha, Antara
AU - Ratia, Kiira
AU - Yin, Liang
AU - Delgado-Rivera, Loruhama
AU - Petukhov, Pavel A.
AU - Thatcher, Gregory R.J.
AU - Wardrop, Duncan J.
N1 - Funding Information:
This study was supported by the National Institutes of Health, National Heart, Lung, and Blood Institute (1UH2HL123610) and the UICentre for drug discovery.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/12/14
Y1 - 2017/12/14
N2 - Hydrogen sulfide is produced from l-cysteine by the action of both cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) and increasingly has been found to play a profound regulatory role in a range of physiological processes. Mounting evidence suggests that upregulation of hydrogen sulfide biosynthesis occurs in several disease states, including rheumatoid arthritis, hypertension, ischemic injury, and sleep-disordered breathing. In addition to being critical tools in our understanding of hydrogen sulfide biology, inhibitors of CSE hold therapeutic potential for the treatment of diseases in which increased levels of this gasotransmitter play a role. We describe the discovery and development of a novel series of potent CSE inhibitors that show increased activity over the benchmark inhibitor and, importantly, display high selectivity for CSE versus CBS.
AB - Hydrogen sulfide is produced from l-cysteine by the action of both cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) and increasingly has been found to play a profound regulatory role in a range of physiological processes. Mounting evidence suggests that upregulation of hydrogen sulfide biosynthesis occurs in several disease states, including rheumatoid arthritis, hypertension, ischemic injury, and sleep-disordered breathing. In addition to being critical tools in our understanding of hydrogen sulfide biology, inhibitors of CSE hold therapeutic potential for the treatment of diseases in which increased levels of this gasotransmitter play a role. We describe the discovery and development of a novel series of potent CSE inhibitors that show increased activity over the benchmark inhibitor and, importantly, display high selectivity for CSE versus CBS.
KW - 2-pyridyl thiosemicarbazones
KW - cystathionine β-synthase
KW - Cystathionine γ-lyase
KW - hydrogen sulfide
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U2 - 10.1021/acsmedchemlett.7b00313
DO - 10.1021/acsmedchemlett.7b00313
M3 - Article
AN - SCOPUS:85038355662
VL - 8
SP - 1241
EP - 1245
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
SN - 1948-5875
IS - 12
ER -